normal Martini topology for drug (fenofibrate)

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1 year 6 months ago #5642 by pela3247
pela3247 created the topic: Martini topology for drug (fenofibrate)
Dear all,

I am trying to create an initial topology for a drug molecule, fenofibrate, and would like your input on what I have so far. I have not started to validate this in any way yet, but comments on the choice of particle types etc. would be much appreciated.

The structure of fenofibrate can be viewed here:
[url=http://https://en.wikipedia.org/wiki/Fenofibrate]Fenofibrate[/url]

I started from the maritini benzene topology for the two rings and modified one of them to accommodate the Cl-atom.

The benzene topology however have [ constraints ] instead of [ bonds ], and I not clear what the best approach would be for me. Combine [ bonds ] for the non-ring particles with the [ constraints ]. Also, are atoms involved in [ constraints ] also involved in [ angles ]?

Below is my starting topology, with everything as [ bonds ].

The particle assignment is as follows:
C2 for the two methyl groups and central carbon
SNa for the O-C=O
P1 for C3-O
SC5, SC5, SC5 for the "first" ring
SNa for the C=O in between the two rings
SC5, SC5, SC3 for the "second" ring.

I am aware that validation is necessary, but how is this for a start?

[ atoms ]
1 C2 1 FEN C2A 1 0
2 SNa 1 FEN SNAB 2 0
3 P1 1 FEN P1C 3 0
4 SC5 1 FEN SC5D 4 0
5 SC5 1 FEN SC5E 5 0
6 SC5 1 FEN SC5F 6 0
7 SNa 1 FEN SNAG 7 0
8 SC5 1 FEN SC5H 8 0
9 SC5 1 FEN SC5I 9 0
10 SC3 1 FEN SC3J 10 0

[bonds]
; i j funct length force.c.
1 2 1 0.47 1250
2 3 1 0.47 1250
3 4 1 0.47 1250
6 7 1 0.47 1250
7 8 1 0.47 1250
4 5 1 0.27 1250
4 6 1 0.27 1250
5 6 1 0.27 1250
8 9 1 0.27 1250
8 10 1 0.27 1250
9 10 1 0.27 1250

[angles]
1 2 3 2 180.0 25.0
2 3 4 2 180.0 25.0
3 4 5 2 130.0 25.0
3 4 6 2 130.0 25.0
5 7 8 2 130.0 25.0
6 7 8 2 130.0 25.0
7 8 9 2 130.0 25.0
7 8 10 2 130.0 25.0

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1 year 6 months ago #5644 by peterkroon
peterkroon replied the topic: Martini topology for drug (fenofibrate)
First you need to define a mapping: What atoms come together to form a bead. Once you have that, do the rest.

This is one of the hardest molecules I have seen to coarse grain, but here's a mapping I came up with - you may have to try multiple:
C3O
(C=O)C3
OC2 (ring1)
C2 (ring1)
C2 (ring1)
(C=O)C (ring2)
C2 (ring2)
C2 (ring2)
CCl (ring2)

(And a second option, which I like slightly less, because of the C=O bead)
C3O
(C=O)
C3OC
C2 (ring1)
C2 (ring1)
C(C=O)C
C2 (ring2)
C2 (ring2)
CCl (ring2)

As for bead types: first guesstimate them based on your gut feeling, and validate it by checking the solvation free energy
As for bonded interactions: rings are usually constrained, since the corresponding force constants are very high. You can view these constraints as normal bonds with an infinitely large force constant.

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1 year 6 months ago #5645 by pela3247
pela3247 replied the topic: Martini topology for drug (fenofibrate)
Hi Peter

Great - thanks for your input, I will use your mapping as an alternative starting point to mine, and proceed from there. Will report back once I have the solvation free energy tests in hand.

Thanks again

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